Device and method for targeted delivery of aerosolized particles to the lungs

ABSTRACT

A nebulizer device includes an air intake port positioned downstream of a nebulizer element, and a mouthpiece positioned upstream of the nebulizer element. A flow sensor is coupled to a controller. The controller is configured to integrate an inhaled air flow signal received from the flow sensor for determining an inhaled air volume. The controller is also configured to turn on the nebulizer element when the inhaled air volume reaches a first predetermined threshold, and turn off the nebulizer element when the inhaled air volume reaches a second predetermined threshold. A method for targeted delivery of aerosolized particles to the lungs is also disclosed.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. provisional application No.62/627,330 filed on Feb. 7, 2018, incorporated herein by reference inits entirety.

BACKGROUND OF THE INVENTION

Effective drug delivery to patients is an important aspect of anysuccessful drug therapy. Certain therapies rely on pulmonary deliverytechniques, which includes inhalation of a pharmaceutical formulation bythe patient so that the drug or active agent within the formulation canreach the lungs. Pulmonary delivery techniques can be particularlyadvantageous for treating certain respiratory related ailments since itallows for selective delivery of pharmaceutical formulations to theairways. Pulmonary delivery techniques also have been known to causeless side effects than traditional systematic administration.

The efficacy of drug delivery can be improved by targeting aerosolizedmedication to certain areas of the lungs. For example, U.S. Pat. No.8,534,277 to Stenzler et al. titled “Device, system and method fortargeting aerosolized particles to a specific area of the lungs”describes a system that can target a specific area of the lungs byaltering aerosol parameters, such as volume, particle size, timing andflow rate. For example, the system introduces particle free air for afirst predefined time period, then introduces a certain amount ofaerosolized particles, followed by a second predefined period of aerosolparticle free air. The object of introducing particle free air in thefirst predefined period is to direct air to the lower regions of thelungs. The object of the second time period of particle free air is toclear the upper region and extrathoracic airway region, respectively,(e.g., mouth, pharynx, and trachea) of the lungs to thereby drive theaerosol bolus to the central region (bronchial) or peripheral region ofthe lungs. In addition to initiating drug delivery based on time,certain prior art devices can also initiate drug delivery based ondetecting a threshold inhalation flow volume. In these systems, once thenebulizer is turned on, the duration of drug delivery is based ondelivering a fixed bolus or fixed volume of drug over a fixed timeinterval.

However, there are certain disadvantages to the prior art systemsdescribed above. For example, once drug delivery is triggered, if apatient is breathing slower and takes more time to reach the stoppingvolume, the nebulizer will deliver excessive amounts of drug sincedelivery is based on a fixed time interval. Conversely, if the patientis breathing fast, the nebulizer will continue to deliver drugs whilethe patient is exhaling, which is wasteful and ineffective, while thepatient receives less than the desired dosage.

Accordingly, there is the need in the art for an improved device thatcan more efficiently and effectively deliver drugs to a patient, takinginto account the real-time variability of inhalation efforts amongdifferent patients, as well as the real-time variability of inhalationefforts of the same patient from breath-to-breath.

SUMMARY OF THE INVENTION

In one embodiment, a nebulizer device includes an air intake portpositioned downstream of a nebulizer element, and a mouthpiecepositioned upstream of the nebulizer element; and a flow sensor coupledto a controller; wherein the controller is configured to integrate aninhaled air flow signal received from the flow sensor for determining aninhaled air volume; wherein the controller is configured to turn on thenebulizer element when the inhaled air volume reaches a firstpredetermined threshold, and wherein the controller is configured toturn off the nebulizer element when the inhaled air volume reaches asecond predetermined threshold. In one embodiment, the predeterminedthreshold is a patient-specific threshold. In one embodiment, thenebulizer device includes a plurality of deposition detection elementsconfigured to mate with a plurality of deposition identificationelements disposed on a removable storage container. In one embodiment,the plurality of deposition detection elements are a plurality ofdetection pins. In one embodiment, the plurality of depositionidentification elements are a plurality of metal contacts connected tothe nebulizer element. In one embodiment, the plurality of depositionidentification elements are indicative of a target deposition areawithin lungs of a patient. In one embodiment, an opening to theremovable storage container is at least partly defined by the nebulizerelement. In one embodiment, the nebulizer element is a nebulizer mesh.In one embodiment, the removable storage container comprises an interiorcup nested within a chamber of the storage container. In one embodiment,the interior cup is in fluid communication with the nebulizer element,and the chamber is not in fluid communication with the nebulizer mesh.In one embodiment, the flow sensor is a single fixed orifice flowsensor. In one embodiment, the flow sensor is a dual orifice flow sensorcomprising a fixed orifice and a variable orifice arranged in parallel.In one embodiment, a one way valve positioned directly over the dualorifice flow sensor configured to permit airflow in an upstreamdirection. In one embodiment, the nebulizer device includes a drip cuppositioned between the mouthpiece and the flow sensor. In oneembodiment, the nebulizer device includes an exhalation valve positionedbetween the mouthpiece and the storage container. In one embodiment, theair intake port is positioned at a base of the nebulizer device housing.In one embodiment, the nebulizer device includes a portable power sourcecoupled to the controller and nebulizer element, and stored within ahousing of the nebulizer device. In one embodiment, the nebulizer deviceincludes a status indicator coupled to the controller and comprising atleast one of a light indicator and an auditory indicator. In oneembodiment, the status indicator is configured to activate when theinhaled air volume reaches the first predetermined threshold. In oneembodiment, the status indicator is configured to activate when theinhaled air volume reaches a second predetermined threshold. In oneembodiment, the nebulizer device is a handheld device.

In one embodiment, a method for targeted delivery of aerosolizedparticles to the lungs includes the steps of determining a depositionidentity from a removable storage container; measuring and integratingan inspiratory flow to determine inspiratory volume; activating anebulizer element when the inspiratory volume reaches a first volumethreshold associated with the deposition identity; and deactivating thenebulizer element when the inspiratory volume reaches a second volumethreshold associated with the deposition identity.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing purposes and features, as well as other purposes andfeatures, will become apparent with reference to the description andaccompanying figures below, which are included to provide anunderstanding of the invention and constitute a part of thespecification, in which like numerals represent like elements, and inwhich:

FIG. 1 is a system diagram of a nebulizer device according to oneembodiment.

FIG. 2 is a perspective view of a nebulizer device resting in a chargingbase according to one embodiment.

FIG. 3 is a side cutaway view of a nebulizer device resting in acharging base according to one embodiment.

FIG. 4A is an isolated and magnified side view of a dual orifice flowsensor according to one embodiment. FIG. 4B is an isolated and magnifiedperspective view of the dual orifice flow sensor shown in FIG. 4A.

FIG. 5 is a perspective cutaway view of a nebulizer device resting in acharging base with the storage container removed from the storagecontainer seat according to one embodiment.

FIG. 6 is a side cutaway view of a storage container according to oneembodiment.

FIGS. 7A-7C are alternate perspective view of a storage containeraccording to one embodiment.

FIG. 8 is a flow chart of a method for targeted delivery of aerosolizedparticles to the lungs according to one embodiment.

DETAILED DESCRIPTION OF THE INVENTION

It is to be understood that the figures and descriptions of the presentinvention have been simplified to illustrate elements that are relevantfor a more clear comprehension of the present invention, whileeliminating, for the purpose of clarity, many other elements found insystems and methods of targeted delivery of aerosolized particles to thelungs. Those of ordinary skill in the art may recognize that otherelements and/or steps are desirable and/or required in implementing thepresent invention. However, because such elements and steps are wellknown in the art, and because they do not facilitate a betterunderstanding of the present invention, a discussion of such elementsand steps is not provided herein. The disclosure herein is directed toall such variations and modifications to such elements and methods knownto those skilled in the art.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although any methods andmaterials similar or equivalent to those described herein can be used inthe practice or testing of the present invention, the preferred methodsand materials are described.

As used herein, each of the following terms has the meaning associatedwith it in this section.

The articles “a” and “an” are used herein to refer to one or to morethan one (i.e., to at least one) of the grammatical object of thearticle. By way of example, “an element” means one element or more thanone element.

“About” as used herein when referring to a measurable value such as anamount, a temporal duration, and the like, is meant to encompassvariations of ±20%, ±10%, ±5%, ±1%, and ±0.1% from the specified value,as such variations are appropriate.

Ranges: throughout this disclosure, various aspects of the invention canbe presented in a range format. It should be understood that thedescription in range format is merely for convenience and brevity andshould not be construed as an inflexible limitation on the scope of theinvention. Where appropriate, the description of a range should beconsidered to have specifically disclosed all the possible subranges aswell as individual numerical values within that range. For example,description of a range such as from 1 to 6 should be considered to havespecifically disclosed subranges such as from 1 to 3, from 1 to 4, from1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well asindividual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5,5.3, and 6. This applies regardless of the breadth of the range.

Referring now in detail to the drawings, in which like referencenumerals indicate like parts or elements throughout the several views,in various embodiments, presented herein is a device and method fortargeted delivery of aerosolized particles to the lungs.

Embodiments of the device trigger drug delivery via nebulization once aninhaled volume is reached, and the device continuously nebulizes for afixed volume of inhaled breath. This represents a significant advantageover prior art devices that nebulize over a fixed time or a fixed volumeof drug. For example, if a patient inhales at a faster than normal rateand reaches the target stopping volume sooner, the embodiments of thedevice described herein will stop nebulizing. This is contrary to priorart devices that nebulize over a fixed time or a fixed volume of drug,and would otherwise continue to nebulize past the target inhaled volume.Thus, in the prior art, subjects can be exhaling while the device isstill nebulizing, whereas embodiments of the device described hereinwould turn off the nebulizer if inhalation stops. Further, embodimentsof the device advantageously take into account an upper airway deadspace volume to clear the upper airway of aerosolized particles.Advantageously, the device is breath actuated, has an orifice flowsensor to measure inspiratory flow, and a vibrating mesh nebulizingelement (which can be instantaneously turned on or off) to produce bolusaerosols. Embodiments of the reservoir medication cup also have multiplepin pairs that can inform the microprocessor as to the depositionpattern for the specific drug loaded in the reservoir. These enable thedevice to deliver the bolus of the aerosol to the periphery, the centralairways, or both the central airways and periphery. In addition, thedevice can include multicolor indicators which light up the device'shead and inform the user of the device status to guide the user throughtheir treatment. Embodiments of the device can individualize and recorddosages based on actual patient respiratory capability and performanceof the particular patient. The device makes delivery of the drugproducts in the exact amounts and lung locations possible, whethercentral, periphery, or both or continuous on inspiration according tophysician's prescriptions. Further, the device can maintain completecompliance with all HIPAA regulations and requirements, and connectionssuch as Bluetooth enable device diagnostics that may be accessed andreviewed remotely.

With reference now to FIG. 1, according to one embodiment, a systemdiagram for a handheld nebulization device 10 includes a removablestorage container 20 that communicates with an ID mechanism 22. Thiscommunication between the removable storage container 20 and IDmechanism relays delivery parameters to the nebulizing element 30 viathe controller 80 for purposes of delivering medication to the properarea of the lungs. In one embodiment, the ID mechanism 22 includes aseries of leads that interact with a pattern of metal contacts on thestorage container 20. For example, in one embodiment, the ID mechanism22 includes a left pair of contacts (contacts 1 and 2) and a right pairof contacts (contacts 3 and 4). One of the left pair of contacts cancomplete a circuit with one of the right pair of contacts, identifyingdifferent values based on which combination of left-pair contacts 1 and2 completes the circuit with right-pair contacts 3 and 4. Sincedifferent electrical signals can be associated with the differentcombinations of connections between the left pair of contacts (contacts1 and 2) and the right pair of contacts (contacts 3 and 4), the patternof metal contacts on the storage container 20 can be set to correspondwith four different drug delivery parameters. The pattern of metalcontacts can communicate with the nebulizing element 30 via thecontroller 80 so that different combinations of connections candifferentiate delivery. This way, embodiments of the device can identifynot only the drug, but specifically where the drug should be deliveredby communicating delivery parameters to the nebulizing element 30.Communication can also be through other means understood in the art,such as in one embodiment, the storage container 20 includes a geometricstructure that mechanically mates with a spring loaded pin structure onthe ID mechanism 22, so that the storage container 20 acts as amechanical key for relaying delivery parameters. In one embodiment, thenebulizing element 30 is an ultrasonic vibrating mesh that can beinstantaneously turned on or off to produce bolus aerosols.

The nebulization device 10 includes a nebulizing element 30 that turnson during inhalation when drug should be introduced into the airstream.A flow rate sensor 40 which in one embodiment is a orifice flow sensormeasures inspiratory flow. In one embodiment, during inspiration, theflow rate sensor 40 measures instantaneous inspiratory flow (which incertain embodiments requires a polynomial equation to calculate flowfrom pressure transducer) and integrates that flow to determine inspiredvolume. Depending on the deposition target in the lungs, the controller80 will instruct when, within the patient's inspiration, the nebulizingelement 30 should be turned on and turned off to deliver bolus aerosolsto the targeted regions. In one embodiment, the device 100 can transmitits operational characteristics and data to a smartphone or tablet inreal-time, and the peripheral device can in turn transmit functionaldata and instructions to the device 100. In one embodiment, the device100 operates independent of a smartphone or tablet peripheral device. Inone embodiment, the volume of upper airway dead space, target inspiredvolume and breath hold time are programmable parameters. In oneembodiment, calculation of volumes at which nebulizer should turn on andoff are based on these programmable parameters and an identification(e.g. via the storage container) of where the drug should be deliveredin the lungs. In one embodiment, the flow rate sensor 40 is a singlefixed orifice flow sensor and does not include a variable orificecomponent. In one embodiment, the flow rate sensor 40 is a dual orificeflow sensor including a fixed orifice and a variable orifice arranged ina parallel structure (described in more detail below with reference toFIGS. 4A and 4B). The fixed orifice provides a low resistance pressuredrop and the variable orifice increases the sensitivity as the flowincreases while providing mechanical effort feedback to the patient thattheir flows are increasing too much.

Status indicators 60 such as visual and/or audio indicators communicatewith the controller 80, for example to tell the patient when to stopinhaling. In one embodiment, the status indicators are color LED lights.For example, if the goal is to deliver the drug to the central airways,the patient can be signaled to stop based on a detected trigger volumeso that they won't keep inhaling to instead draw the drug into theperiphery. In one embodiment, the device has a red-green-blue (RGB) LEDfor status indication. For example, in one embodiment, the LED blinksrapid blue while searching for pairing. In one embodiment, the LEDblinks red for 5 seconds and then turns the device off if the battery islow. In one embodiment, the LED blinks green slowly when the patient canstart an inhalation. In one embodiment, the LED illuminates solid greenduring an inhalation period. In one embodiment, the LED illuminatessolid red during a breath hold period. In one embodiment, the LED turnsoff when the patient can exhale. In one embodiment, the LED blinks redslowly for 5 seconds when the reservoir is empty and the treatment iscomplete. In one embodiment, the user is able to view the RGB LED whileoperating the device and breathing on the mouthpiece 50. In oneembodiment, the device has an audible tone generator to beep twice onpairing, once on start of breath hold and once on start of exhalation.Advantageously, embodiments of the device include indications based ondetected inhaled volume to have the patient stop inhaling. Components ofthe device can be powered by a removable or rechargeable power source70, such as a rechargeable battery.

With reference to FIGS. 2 and 3, a nebulizer device 100 is shown restingin a charging base 190 according to one embodiment. The nebulizer device100 includes an external wall 104, a mouthpiece 150 for the patient tobreath on, an exhalation valve 102 downstream of the mouthpiece 150, anda storage container 120 downstream of the exhalation valve 102. Thedevice 100 is designed so that the patient can inhale and exhale overseveral cycles without removing the device 100 from their mouth. Duringexhalation, air flows out of the exhalation valve 102. There is also aone way valve 146 upstream and directly on top of the variable orificeflowmeter 140 that closes during exhalation and only permits theupstream flow of air. A drip cup 106 is positioned between themouthpiece and one way valve to divert saliva and further protect thefunction of the variable orifice flowmeter 140, while also minimizingthe risk for contaminating the storage container 120. During inhalation,room air flows upstream through the air intake port 108 and variableorifice flowmeter 140. The one way valve 146 is open during inhalation.A pressure transducer measures pressure at the variable orificeflowmeter 140 to calculate flow, which is then integrated by thecontroller 180 to volume. Deposition detection pins 114 communicate withthe controller 180 to determine when the nebulizer mesh 130 should turnon or off, based on the configuration/instruction detected by the pins114 and the volume calculated by the controller 180. In one embodiment,the nebulizer device 100 has four pins. As should be understood by thosehaving ordinary skill in the art, the nebulizer can have 2, 3, 4, 5 ormore pins, depending at least partially on the number of differentdelivery parameters desired by the system, and the number of pincombinations required to accommodate that number of delivery parameters.The system is powered by a rechargeable battery power source 170 thatcharges via contact with the charging base 190. The charging base 190can also include a USB connection 192 for providing power or forupdating firmware of the device 100.

In one embodiment, as shown with greater detail in FIGS. 4A and 4B, thevariable orifice flowmeter 140 is a dual orifice flow sensor including afixed orifice 142 and a variable orifice 144 arranged in a parallelstructure. A one way valve 146 is positioned upstream and directly ontop of the variable orifice flowmeter 140, in fluid communication withboth the fixed orifice 142 and the variable orifice 144. The one wayvalve 146 closes during exhalation and only permits the upstream flow ofair during inhalation. In one embodiment, the variable orifice 144 is apressure actuated valve, such as a silicone duckbill valve or slitvalve. The fixed orifice 142 provides a low resistance pressure dropwhile the variable orifice 144 increases the sensitivity as the flowincreases while providing mechanical effort feedback to the patient thattheir flows are increasing too much. In one embodiment, the flowmeter140 is strictly a fixed orifice flowmeter and does not include avariable orifice component.

With reference now to FIG. 5, the nebulizer device 100 is shown with thestorage container 120 removed from the storage container seat 112.Deposition detection pins 114 are shown in a bottom portion of thestorage container seat 112. As illustrated, the deposition detectionpins 114 access the storage container seat 112 so that they can matewith the corresponding deposition identity pins 125 connected to thenebulizer mesh 130 of the storage container 120, as illustrated in FIGS.6-7C. As described above, the pin arrangement can include a left pair ofcontacts (contacts 1 and 2) that completes a circuit with a right pairof contacts (contacts 3 and 4). Since different electrical signals canbe associated with the different combinations of connections between theleft pair of contacts and the right pair of contacts, the pattern ofcontacts on the storage container can be set to correspond withdifferent drug delivery parameters. With reference now to FIGS. 6-7C,the storage container 120 features multiple deposition identity pins 125connected to the nebulizer mesh 130 and keyed to the desired target inthe lungs for the patient and/or medicament that will be stored in thestorage container. The storage container includes a housing 121, a lid122 for accessing the interior chamber 123 of the housing 121, and aninterior cup 124 disposed within the interior chamber 123. A nebulizermesh 130 covers an opening 132 to the housing 121. In one embodiment,the storage container 120 includes an interior cup, or what could bereferred to as a “cup within a cup”. The medications typically come in aprefilled ampule that may contain for example between 2 and 5 mL. If thephysician prescribes 1 mL or 3 mL, it could be difficult for somepatients to place the exact amount into the cup, even with visual lineson the cup. Therefore certain embodiments include a series of insertinterior cups 124 that limit the volume of liquid in front of thenebulizing mesh and pouring in more medication would cause it tooverflow into the storage container chamber 123. Medication in thestorage container chamber 123 will simply be retained for later use ordiscarding. Advantageously, the medication in the storage containerchamber 123 will not be in communication with the mesh foraerosolization, and the patient avoids unintentional overmedication thatcommonly occurs from loading error.

A method for targeted delivery of aerosolized particles to the lungs 200according to one embodiment is shown in the flow chart of FIG. 8. First,a deposition identity is determined based on a characteristic of astorage container 201. The deposition identity is based at leastpartially on a deposition target within the lungs of the patient. Next,inspiratory flow is measured from the patient's inhalation effort, andthis value is integrated to determine total inspiratory volume 202.Based on the previously determined deposition identity and thecalculated inspiratory volume, the nebulizer is activated once theappropriate first threshold is triggered 203. Finally, also based on thepreviously determined deposition identity and the calculated inspiratoryvolume, the nebulizer is deactivated on the appropriate second thresholdis triggered 204.

Experimental Examples

The invention is now described with reference to the following Examples.These Examples are provided for the purpose of illustration only and theinvention should in no way be construed as being limited to theseExamples, but rather should be construed to encompass any and allvariations which become evident as a result of the teaching providedherein.

Without further description, it is believed that one of ordinary skillin the art can, using the preceding description and the followingillustrative examples, make and utilize the present invention andpractice the claimed methods. The following working examples therefore,specifically point out the preferred embodiments of the presentinvention, and are not to be construed as limiting in any way theremainder of the disclosure.

In one example control process, the parameters that would be used by thenebulizer to control the nebulization include:

IV—Predicted/targeted inspired volume (Range 100-5000 mL, Default 800mL); DS—Upper airway clearance volume (oropharyngeal volume) (Range20-300 mL, Default 150 mL); BH—Breath-hold time (Range 0 to 9 seconds,Default 0.5 seconds); BI—Breath Interval (range 3 to 8 seconds, Default4 seconds) and Drug Deposition target (periphery, central, both, orcontinuous).

The first three parameters (IV, DS and BH) have default settings whilethe deposition target is determined by the medication reservoirselected. The settable parameters are stored in non-volatile RAM and canbe changed via the Bluetooth radio by the operator through thesmartphone or tablet application. Once changed, these settings willremain as set in the RAM until changed again.

During inspiration, the nebulizer measures instantaneous inspiratoryflow (requires polynomial equation to calculate flow from pressuretransducer) and integrates that flow to inspired volume. Depending onthe deposition target, the nebulizer will determine when, within thepatient's inspiration, that the nebulizer should be turned on and turnedoff to deliver bolus aerosols to the targeted regions.

The nebulizer will determine the volume at which the nebulizer is turnedon and turned off based on the following parameters:

1. For peripheral deposition: Nebulization started immediately upondetection of inspiration and turns off once the inspired volume reachesthe set IV×0.5.

2. For central deposition: Nebulization starts when the volume reaches(IV−DS)×0.5 and stops when the inspired volume reaches IV−DS−100 mL.

3. For depositing in both: Nebulization starts immediately upondetection of inspiration and turns off once the inspired volume reachesIV−DS−100 mL.

The DAD shall have an audible tone generator to beep twice on pairing,once on ready for inhalation and once on start of breath hold.

The operational steps for the nebulizer are as follows:

1. Turn on power. (Note: Press and holding the power button turns systemoff)

2. Check battery level.

3. If battery is above a threshold voltage, LED rapidly blinks bluewhile searching for application pairing.

a. Upon pairing tone generator beeps twice and LED turns solid green.

b. After 30 seconds of searching without finding the targeted Bluetoothradio, change to a slow blink green and then read the drug containerpins and go to inhalation ready.

4. If battery is low, LED rapidly blinks red and the tone generatorbeeps three times, transmits the low battery status to the applicationand then turns off.

5. Microprocessor reads the set DS, IV, s2 BI and BH.

6. Microprocessor reads the reservoir pins to determine the targetedregion.

a. Calculates the nebulizer start and stop volumes.

7. LED blinks green slowly and the tone generator beeps once when thepatient can start an inhalation.

8. As patient inhales, LED turns solid green, transmits an inhalationflag, and microprocessor integrates flow to volume.

a. Transmit continuous volume to application.

b. Turns nebulizer on and off at the calculated volumes.

c. At the targeted IV, transmit an IV flag, the audio tone beeps onceand the LED will turn red for the duration of the BH time and then theLED will turn off.

9. The LED will turn blinking green again and the tone generator willbeep once after the BI has timed out to indicate when another breath isready to be taken and transmit an “inhalation” flag.

10. Once the microprocessor receives a signal that the reservoir isempty.

a. The microprocessor should transmit the treatment data consisting ofthe duration of the treatment and the number of breaths.

b. Then the LED should blink red for 5 and the tone generator will beepthree times and the device should turn off.

Variations to the control process can for example include: In oneembodiment, an optional operational process could include a learningmode whereby the first few breaths (e.g. five breaths) are taken withouttargets or nebulization. The average of these five breaths is then usedto determine the target inhaled volume and the aerosolization timingdetermined based on that volume. In one embodiment, the microprocessorwill monitor the nebulizer electronics for error codes, battery status,failures, empty drug container, etc., and transmit these to theapplication. In one embodiment, if inspiration stops during the expectedinspiratory time, the nebulization will stop. In one embodiment, theaverage of actual inspired volumes from the current treatment shouldreplace the target IV in the non-volatile RAM for the next treatment. Inone embodiment, treatment parameters such as BH, starting IV, BI, and DScan be programmed by using the software application. In one embodiment,firmware is upgraded via the USB connector. In one embodiment, when thedevice is placed in the charging station, LED indicators can be turnedon white until the battery level is above a threshold voltage and thenthe LED should be turned off.

In one example, during delivery mode, a pairing device such as a mobileor handheld smart device pairs with the controller of the nebulizerusing a pre-configured pairing address such as a media access control(MAC) address. On successful pairing, the nebulizer controller collectspatient and specific delivery settings from the paired device and bothoperate paired. On unsuccessful pairing, the nebulizer controllercontinues using the last programmed delivery settings or a defaultdelivery setting and operates unpaired. Starting operation, thecontroller of the nebulizer activates an aerosolization mode and startsthe detection of inhalation. The nebulizer indicates the start ofinhalation. The nebulizer then activates the breath hold period per theuser setting upon inhalation. Next, the nebulizer then starts a timer atthe end of the breath hold period per the breath hold time user setting.Next, the nebulizer indicates it is ready for the start of a new breathwhen the timer reaches the breath interval time per user setting. Thenebulizer stops aerosolization if inspiration stops during the expectedinspiratory time and starts a breath hold period. The nebulizercontinuously transmits the status of the aerosolization to the paireddevice throughout the process.

Additional functionality of the nebulizer in one example includes: thecontroller turns the nebulizer off when the battery level is below therequirement for delivery of a time duration treatment, e.g. a fifteenminute treatment; the controller of the nebulizer monitors the nebulizerelectronics for error codes, battery status, failures, etc. and transmitthese to the paired device; the controller of the nebulizer stores theinhaled volumes for each breath during the treatment and calculates theaverage inhaled volume; and the controller of the nebulizer replaces thetarget inhaled volume with the averaged inhaled volume from the previoustreatment.

In one example, the controller interacts with the drug container to readthe drug container information off a 4 pin sensing mechanism; send thedrug container information to a paired Bluetooth device upon request;check the drug container pins to determine the aerosol delivery mode;stop aerosolization and turn off the nebulizer when it is detected thatthe drug container is empty; and prohibit aerosolization if the drugcontainer is not detected or cannot read a proper pin combination.

In one example, the aerosol delivery mode is set on the controller toutilize a pressure sensor to calculate flow in mL/minute based on apolynomial equation or lookup table, and integrate the flow to calculatevolume in mL. In one example, the aerosol delivery mode is set on thecontroller based on received aerosolization related specifications fromthe paired Bluetooth device, such as: dead space volume (Range 20-300mL) and default value 150 mL; target inhaled volume (Range 100-5000 mL)and default value 800 mL; breath hold time (Range 0-9000 ms) and default500 ms; breath interval time (Range 3000-8000 ms) (i.e., period from endof breath hold to ready for next inhalation) and default 4000 ms.

The disclosures of each and every patent, patent application, andpublication cited herein are hereby incorporated herein by reference intheir entirety. While this invention has been disclosed with referenceto specific embodiments, it is apparent that other embodiments andvariations of this invention may be devised by others skilled in the artwithout departing from the true spirit and scope of the invention.

What is claimed is:
 1. A nebulizer device comprising: an air intake portpositioned downstream of a nebulizer element, and a mouthpiecepositioned upstream of the nebulizer element; and a flow control sensorcoupled to a controller, the flow control sensor comprising a fixedorifice and a variable orifice arranged in parallel; wherein thecontroller is configured to integrate an inhaled air flow signalreceived from the flow control sensor for determining an inhaled airvolume; wherein the controller is configured to turn on the nebulizerelement when the inhaled air volume reaches a first predeterminedthreshold, and wherein the controller is configured to turn off thenebulizer element when the inhaled air volume reaches a secondpredetermined threshold.
 2. The nebulizer device of claim 1, wherein atleast one of the first predetermined threshold and the secondpredetermined threshold is a patient-specific threshold.
 3. Thenebulizer device of claim 1 further comprising: a removable storagecontainer, the nebulizer device comprising a plurality of depositiondetection elements configured to mate with a plurality of depositionidentification elements disposed on the removable storage container. 4.The nebulizer device of claim 3, wherein the plurality of depositiondetection elements are a plurality of detection pins.
 5. The nebulizerdevice of claim 3, wherein the plurality of deposition identificationelements are a plurality of metal contacts connected to the nebulizerelement.
 6. The nebulizer device of claim 5, wherein the plurality ofdeposition identification elements are indicative of a target depositionarea within lungs of a patient.
 7. The nebulizer device of claim 3,wherein an opening to the removable storage container is at least partlydefined by the nebulizer element.
 8. The nebulizer device of claim 7,wherein the nebulizer element is a nebulizer mesh.
 9. The nebulizerdevice of claim 3, wherein the removable storage container comprises aninterior cup nested within a chamber of the removable storage container.10. The nebulizer device of claim 1 further comprising a one way valvepositioned directly over the flow control sensor configured to permitairflow only in an upstream direction.
 11. The nebulizer device of claim1 further comprising: a drip cup positioned between the mouthpiece andthe flow control sensor.
 12. The nebulizer device of claim 1 furthercomprising: an exhalation valve positioned between the mouthpiece andthe storage container.
 13. The nebulizer device of claim 1 furthercomprising: a portable power source coupled to the controller andnebulizer element, and stored within a housing of the nebulizer device.14. The nebulizer device of claim 1 further comprising: a statusindicator coupled to the controller and comprising at least one of alight indicator and an auditory indicator.
 15. The nebulizer device ofclaim 14, wherein the status indicator is configured to activate whenthe inhaled air volume reaches the first predetermined threshold. 16.The nebulizer device of claim 13, wherein the status indicator isconfigured to activate when the inhaled air volume reaches a secondpredetermined threshold.
 17. The nebulizer device of claim 13, whereinthe nebulizer device is a handheld device.
 18. A method for targeteddelivery of aerosolized particles to the lungs comprising: providing thenebulizer device of claim 1; determining a deposition identity from theremovable storage container; measuring and integrating an inspiratoryflow to determine inspiratory volume; activating the nebulizer elementwhen the inspiratory volume reaches a first volume threshold associatedwith the deposition identity; and deactivating the nebulizer elementwhen the inspiratory volume reaches a second volume threshold associatedwith the deposition identity.
 19. The nebulizer device of claim 1,wherein the variable orifice is configured to increase resistancesensitivity as airflow increases.